Research

A NOVEL NEURO-CORTICAL COUPLING UNRAVELED IN OLFACTORY-VISUAL SACCADIC PATHWAY

Valencia Brown, Imran shareef Syed, Ganesh Elumalai, Nneoma Osakwe, hari krishna golla, Nadira Sewram, Harshita Chatterjee, Pradeep Chandrasekhar, Nitya Akarsha Surya Venkat Ghanta, Lekesha Sobers, MOJESS NANDURI


Abstract

This confirmatory study aims to unravel the neural structural connectivity of “Olfactory-Saccadic pathways” extending between “Piriform and Entorhinal Cortices to Frontal Eye Field (FEF),” and to correlate its functional importance with possible clinical implications, using “Diffusion Imaging fibre Tractography”. The confirmatory observational analysis used thirty-two healthy adults’ ultra-high b-value, diffusion imaging datasets from an Open access platform in Human Connectome Project (HCP) [17]. In all the datasets from both the sexes, fibres were traced and the neural structural connectivity was confirmed. The hemispheric differences between male and female subjects were analysed using independent sample t-test. Thus, the study confirmed the structural existences of Olfactory-saccadic pathways that may be involved in influencing the movements of the neck and eyeball gaze (saccadic eye movement), towards the spatial orientation of olfactory stimulus.

 

Introduction

Saccadic eye movement can be described as a visual process that can be achieved by orienting the eyes towards an object due to influence from a particular stimulus, a process controlled by CNS [16]. The olfactory-visual saccadic pathway is a new structural finding observed by our “Team Neuron”. On an attempt to trace the neural structural connectivity of Olfactory- motor pathways, we identified new structural connections between the “Piriform and Entorhinal Cortex (Brodmann's area 27, 28 and 34) to Frontal Eye Field (FEF)” (Brodmann's area 8). Previous evidences on these hypothetical streams remain unclear, hence we pursued these connections to confirm their structural existence, to identify their possible functional and clinical correlations [2, 3, 4].

FEF participates in the transformation of visual signals into saccades in conjunction with the supplementary eye fields, insula, and median part of the cingulate gyrus. Both the superior colliculus and the frontal eye field (Brodmann's area 8) are the gaze centres, important for the initiation and accurate targeting of saccadic eye movements [12].  There has been evidence to suggest that vision drives olfactory perception, but there has been little indication that olfaction could modulate visual perception [3]. Shenbing Kuang & Tao Zhang performed a test to extend their understanding on vision-olfaction couplings and suggested that a functional interaction between the visual dorsal pathway and the olfactory system exists [4].

When an odour approaches from an unknown distance and from an unknown direction, it can still be perceived without looking, hence one can perceive, detect, discriminate and identify a given olfactory stimulus, then our eyes engage in rapid movement (saccadic eye movement) towards the localized stimulus for fixation [3, 4]. So, according to our hypothesis, we are suggesting that there exists some structural connectivity between the primary olfactory cortex to the frontal eye field and in case of any damage to this connectivity, it may lead to olfactory attention deficit. Olfactory impairments, as described in various neurodegenerative and psychiatric disorder, lead to deficits in the detection, discrimination, and identification of odours; therefore,  they are likely to share affected brain anatomical substrates with Alzheimer’s disease, Parkinson’s disease, Obsessive-compulsive disorder (OCD), Schizophrenia, Huntington’s Disease and multiple sclerosis among others [1, 5].

 

Materials and Methods

The study used open access datasets of ultra-high b-value and various diffusion sensitizing direction diffusion imaging software with the in-plane resolution and slice thickness of 1.5 mm. The datasets are originally developed and reposted by Massachusetts General Hospital – US Consortium Human Connectome Project (MGH-USC HCP). The study involves Thirty-two healthy adult datasets (16 male and 16 female, between the ages of 20–59 years old, mean age = 30.4). Given de-identification considerations, age information is provided in 5-year age bins (Table-1). All participants gave written informed consent, and the experiments were carried out with approval from the Institutional Review Board of Partners Healthcare of MGH-USC HCP project [17].

Subject No.

Age (yrs)

No. of male subject

No. of female subject

1

20-24

1

5

2

25-29

6

8

3

30-34

5

0

4

35-39

3

1

5

40-44

2

1

6

45-59

2

1

 

TOTAL

16

16

      Table 1 shows age information of male and female subjects

Fig. 1 Shows Coronal sections of right side of female and male brain fibres respectively in olfactory-saccadic pathway

 

Results

Fibre tracking datasets were collected from 32 subjects, data which confirmed the existence of a structural connectivity between the Piriform and Entorhinal cortices and the frontal eye field. The datasets were analysed within the following parameters:

(A)-Number of tracts,

(B)-Tract volume (mm3)

(C)-Tract length mean (mm)

(D)-Tract length standard deviation (mm)

Variances within the parameters observed were also evaluated among male and female subjects. According to our secondary hypothesis, we theorized that similarities would be observed in the connectivity that exist within the hemispheres with respect to each sex and also when compared between both sexes which was observed, overall, statistically significant findings were seen.

 

Discussion

Saccades can be initiated by peripheral stimuli through uni-modal sensory interaction but are most times influenced by the interaction of multisensory signals where the potential target exudes signals from sensory modality interaction based on visual, auditory and even tactile inputs [8, 12]. The influence of these associations on the production of saccades individually have been widely explored, predominantly establishing neural connectivity between auditory and visual pathways anatomically and functionally but such studies pertaining to olfactory-visual associations had yet to discover anatomical and functional links between both pathways [7]. Auditory and visual sensory stimulations recorded by electroencephalogram (EEG) in an experiment conducted by Kirchner, H. et al (2009) provided evidence that the FEF is not limited to eliciting saccades purely based on visual stimulations but found evidence that the FEF responded to auditory and visual stimulation within a similar scope suggesting that the FEF processes multimodal signals [2, 6]. In light of this finding, we hypothesized and explored a possible structural connection between the FEF and the olfactory cortices.

Based on studies carried out by Judauji, J. et al (2012) and Morrot, G. et al (2001), which investigated to what extent visual cues could affect olfactory processing through visual-olfactory associations, we deduced that visual cues directly influences odor identification, perception and also attention [10]. Alternatively, studies conducted by Kuang, S. and Zhang, T. (2014) and  Harvey, C. (2018) examined cross-modal integration in olfactory-visual coupling and found that olfactory cues influence gaze shifts and visual attention finding a functional pathway with which odor stimuli can initiate and guide eye movements [9]. These studies made implications of a functional association between odor and visual pathways, but the structural associations remained undiscovered [14, 15].

Our data demonstrates a new finding that structural connectivity exists between the ventral and dorsal Entorhinal cortex (Brodmann area 28 (V) & 34 (D), Piriform cortex (Brodmann area 27) and the Frontal eye field (Brodmann area 8), hence supporting previous documentation that suggested that olfactory cues could modulate visual attention, prompting saccades leading to spatial perception through neck and eye movements towards the stimuli [3, 4]. These new findings were discovered through non-invasive imaging methods where brain fibres were traced using diffusion tensor imaging from magnetic resonance imaging (MRI) data collected from both male and female subjects.  The results suggest that the findings of this study are mainly significant within the population and supported our initial conjecture. The data collected within the population generally showed consistent results in the parameters observed which were number of tracts, tract volume, tract length mean and tract length standard deviation in male and female subjects on both left and right brain hemispheres. For the most part the difference in the data collected for males and females deemed insignificant. However, slight variance was observed among some variables deviating from our subsidiary hypothesis where we suggested that general hemispheric similarities would be maintain when comparing between the parameters observed.  It was observed among male subjects that on average, the right side had a greater number of tracts than the left side and it was also seen that female subjects had a greater number of tracts than male subjects on the left side. These results have now unravelled a novel neuro-cortical pathway anatomically that fortifies studies that have previously indicated olfactory-visual coupling through cross-modal interaction between the senses [2, 3, 10, 11].

In converging the data of this study, the findings were deemed significant; however, we were minimally limited in the sample size and diversity in randomness of collection of data within the population. In future research, a larger sample size could be explored with additional parameters and variables such as imaging of the neuropathology of the structural pathway discovered. Also, since our topic of study is rather contemporary, literature to directly support the scope of our study was sparse and this report should then serve as a window to explore this topic further.

In light of these findings, additional functional and clinical correlations can be deduced as a potential bio-marker for evaluating and assessing certain neurodegenerative and psychiatric disorders where olfactory attention deficits are manifested as early onset of such disorders [1, 5]. Oftentimes, olfaction is referred to as the vestigial sense and as one study showed, it can be observed that olfactory function is given little evaluation in routine clinical examination, hence minimal importance is placed on the fact that olfaction can provide conclusive assessments for cognitive function [1, 9, 13]. A decline in olfactory function has been found to be an initial symptom of numerous neurodegenerative disorders such as Alzheimer’s, and Parkinson’s disease. Hence, early identification of olfactory functional deficit can serve as an initial symptom for differential diagnostic purposes with the ability to assess and evaluate strategies and therapies that can provide neuroprotective properties. This new structural connectivity found between the olfactory and visual pathway can be used in advancing neuroimaging technique for diagnostic purposes in evaluating cognitive decline and progression of disease [1, 9].

Further research could focus on identifying and evaluating alterations in the structural integrity of the olfactory-visual pathway in patients that suffer from certain neurodegenerative diseases, as such diseases makes them susceptible to olfactory attention deficits and also the exact causes and pathological actions that lead to olfactory dysfunction in these diseases since the concept remains unclear [1, 9]. These findings should draw more attention toward how critical olfactory function assessment is in the clinical setting. We publish this in hopes that these findings are further supported since olfactory function evaluation could possibly predict neuro-aging deficit predisposition and assess cognitive decline.

 

Glossary

Brodmann area- a region of the cerebral cortex, defined by its histological structure and organization of cells.

Cortical- relating to, associated with, or depending on the cerebral cortex.

Entorhinal cortex- is an area of the brain located in the medial temporal lobe, functioning as a hub in a widespread network for memory, navigation and the perception of time.

Neuro- relating to nerves or the nervous system.

Piriform cortex- relating to the part of the cerebral cortex that receives primary input from the olfactory bulb.

Saccade- a small rapid jerky movement of the eye especially as it jumps from fixation on one point to another.

Team Neuron- organized exclusively for neuroscience and related neuroscientific research guiding purpose, mainly focusing on guiding the Basic and Clinical Neuroscience research activities among the young research scholars.


References


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Valencia Brown

Valencia Brown


Valencia Brown is a medical student and also a young researcher who studies at the Texila American University in Guyana, and has main interest in the area of neuroscience and its related topics.

Imran shareef Syed

Imran shareef Syed


This author has not yet uploaded a bio.

Ganesh Elumalai

Ganesh Elumalai


This author has not yet uploaded a bio.

Nneoma Osakwe

Nneoma Osakwe


This author has not yet uploaded a bio.

hari krishna golla

hari krishna golla


This author has not yet uploaded a bio.

Nadira Sewram

Nadira Sewram


Junior Researcher - Department of Neuroscience, Texila American University (Guyana Campus)

Harshita Chatterjee

Harshita Chatterjee


This author has not yet uploaded a bio.

Pradeep Chandrasekhar

Pradeep Chandrasekhar


This author has not yet uploaded a bio.

Nitya Akarsha Surya Venkat Ghanta

Nitya Akarsha Surya Venkat Ghanta


Nitya Akarsha Surya Venkat Ghanta,M.D.

Lekesha Sobers

Lekesha Sobers


Guyanese/Saint Lucian BSc. Medical Technology Medical Student

MOJESS NANDURI

MOJESS NANDURI


This author has not yet uploaded a bio.